Cyclization aryl radical

The data from Beckwith s work given in Table 10-9 look very confusing but, as discussed in the four papers by Beckwith s group (see footnote a) in Table 10-9) and in additional comments in Galli s review (1988), they can all be explained on the basis of our present knowledge of aryl radical chemistry, with the exception of the endo cyclization of the 2-(7V-2,-propenylsulfamoyl)-benzenediazonium ion in Scheme 10-81. 

The N,0- and N,S-heterocyclic fused ring products 47 were also synthesized under radical chain conditions (Reaction 53). Ketene acetals 46 readily underwent stereocontrolled aryl radical cyclizations on treatment with (TMSlsSiH under standard conditions to afford the central six-membered rings.The tertiary N,0- and N,S-radicals formed on aryl radical reaction at the ketene-N,X(X = O, S)-acetal double bond appear to have reasonable stability. The stereoselectivity in hydrogen abstractions by these intermediate radicals from (TMSlsSiH was investigated and found to provide higher selectivities than BusSnH. 

The C-Se and C-Te bonds are formed by an internal homolytic substitution of vinyl or aryl radicals at selenium or tellurium with the preparation of selenophenes and tellurophenes, respectively. An example is shown below, where (TMSIsSiH was used in the cyclization of vinyl iodide 65 that affords... 

Evidence for the formation of alkyl and aryl radicals in some cases following loss of SO2 (Scheme 1) has been obtained. Thus, a small amount of M-pentane was formed in the decomposition of M-pentanesulphonyl azide in mineral oil ). Thermolysis of diphenyl sulphone-2-sulphonyl azide (8) in dodecane at 150 °C gave diphenyl sulphone 9 (27%) and diphenyl sulphone-2-sulphonamide 10 (9%) which arise by hydrogen abstraction by the aryl radical and sulphonyl nitrene, respectively. When this thermolysis was carried out in Freon E-4 at 150 °C, the products were diphenylene sulphone 77 (1.3%) (Pshorr-type cyclization product of the aryl radical) and 10 (1.5%) together with tars 16h Ferro-... 

Radical cyclization of acyclic sulfinamides 239 provides easy access to cyclic sulfinamides 241 <06AG(E)633>. Conceivably, the reaction pathway involves thiophilic attack by the aryl radical with a concomitant or successive expulsion of the p-tolyl or tert-butyl radical. 

Partially saturated derivatives can also be prepared through aryl radical cyclization of A-2-halobenzoyl cyclic ketene-iVA-acetals <2005TL3801>. In this event, treatment of ketene-acetal 418 with Bu3SnH afforded good yield of cyclized products 419 and 420, as a mixture of two diastereoisomers, but with a total regioselectivity (Scheme 108). 

The diketone 64 was also readily prepared from 59 as outlined in Scheme 20.15. Condensation between 64 and 2 equiv. of 51b gave 65 in excellent yield. Thermolysis of 65 in 1,4-CHD at 75 °C also promoted the Myers-Saito cyclization reaction to generate the biradical 66. The aryl radical center in 66 was then captured by the allenic moiety to form 67, having two stabilized triarylmethyl radical centers. Subsequent hydrogen-atom abstractions from 1,4-CHD then furnished 68. 

The benzannulated analogs were also found to behave in a similar fashion. Attachment of a pendent olefin to the benzannulated enyne-allene system as depicted in 89 allowed the aryl radical in 90 to be captured in a 5-exo radical cyclization reaction leading to 91 and then the dihydrobenz[e]indene 92 (Scheme 20.20) [55, 56]. 

Free-radical cyclization on to unsaturated CN bonds and also the cyclization of a range of nitrogen-centred radicals have continued to attract interest and have been reviewed. Aryl radicals, generated from BusSnH- or TTMSS-mediated homolytic cleavage of aryl-bromide bonds, have been shown to cyclize on to the nitrogen atom of imidate esters in the 5-exo mode (Scheme 9). Loss of an ethyl radical leads to the observed A-acylindolines. No cyclization in the 6-endo mode was detected. 

Thermolysis of benzoenyneallene (113) in cyclohexadiene at 75 °C produced the cycloaromatized adduct (116) in 22% yield. A biradical is believed to form through a cascade sequence involving an initial Myers cyclization. Trapping of the aryl radical centre in (114) with the tetrarylallenic moiety intramolecularly affords (115), having two triaryl radical centres. Hydrogen abstraction from cyclohexa-1,4-diene by (115)... 

A convenient preparation of dihydrobenzofurans has been achieved from the appropriately functionalized ort/ o-halophenol derivatives. Treatment of the aryl iodide (5)-33 with (TMS)3SiH and EtsB in the presence of air at room temperature, gave the aryl radical which cyclized in a 5-exo-trig mode and provided the bicyclic derivatives 34/35 as a 29 1 mixture of diastereoisomers in favour of 34 (Reaction 7.40) [51]. 

The aryl radical cyclization has been successfully used for the preparation of substituted dihydrobenzo[Z)]indoline derivatives [59], An example is shown in Reaction (7.49). The diene 42 was preliminarly subjected to ring-closure metathesis using Grubbs catalyst and then treated with (TMS)3SiH and EtsB at -20 °C, in the presence of air, to provide the compound 43 with an excellent diastereoselectivity. 

For the synthesis of tricyclic isoindolinones, the 5-exo-trig cyclization of aryl radicals has been applied [69]. Reaction (7.59) shows the example of a tricyclic system obtained in a 71 % yield. 

In model studies directed towards the synthesis of ( )-gelsemine, 5-exo-trig cyclization of an aryl radical, derived from the vinylogous uretane 58, onto a methoxymethyl enolether resulted in partial fragmentation of the intermediate... 

The plan for a tandem cyclization as the key step in the synthesis of morphine alkaloids has been successfully performed [95]. Three examples are given in Scheme 7.10. Specifically, the initially formed aryl radical, generated by bromine abstraction from compound 74, underwent a tandem cyclization to construct the desired carbocyclic skeleton. Depending on the nature of the Z substituent to the double bond, the product radicals either abstracted hydrogen from silane (Z = C02Me or CN) or eliminated thiyl radical (Z = SPh). 

Crich and Rumthao reported a new synthesis of carbazomycin B using a benzeneselenol-catalyzed, stannane-mediated addition of an aryl radical to the functionalized iodocarbamate 835, followed by cyclization and dehydrogenative aromatization (622). The iodocarbamate 835 required for the key radical reaction was obtained from the nitrophenol 784 (609) (see Scheme 5.85). lodination of 784, followed by acetylation, afforded 3,4-dimethyl-6-iodo-2-methoxy-5-nitrophenyl acetate 834. Reduction of 834 with iron and ferric chloride in acetic acid, followed by reaction with methyl chloroformate, led to the iodocarbamate 835. Reaction of 835 and diphenyl diselenide in refluxing benzene with tributyltin hydride and azobisisobutyronitrile (AIBN) gave the adduct 836 in 40% yield, along with 8% of the recovered substrate and 12% of the deiodinated carbamate 837. Treatment of 836 with phenylselenenyl bromide in dichloromethane afforded the phenylselenenyltetrahydrocarbazole 838. Oxidative... 

Aryl diazonium ions are converted to iodides in high yield by reaction with iodide salts. This reaction is initiated by reduction of the diazonium ion by iodide. The aryl radical then abstracts iodine from either I2 or I3. A chain mechanism then proceeds which consumes I- and ArN2+.105 Evidence for the involvement of radicals includes the isolation of cyclized products from o-allyl derivatives. 

Intramolecular group-transfer reactions can involve either direct displacements or addition-fragmentation reactions that are discussed in Section 4.2.4. A direct displacement is shown in the reaction of aryl radical 1, produced from the corresponding bromide. Cyclization of 1 is fast enough to compete efficiently... 

Allyloxy)iodoarenes react with Sml2 to yield radical anions, which undergo thermal fragmentation. The resulting aryl radicals can cyclize to dihydrobenzofurans (Entries 8-10, Table 15.9). The radical obtained after cyclization can be reduced and treated with a proton source such as water or an alcohol to yield alkanes, or with carbonyl compounds to yield alcohols (Entry 10, Table 15.9). 

Formation of cyclized products, resulting from intramolecular attack of the intermediate aryl radical in the SrnI reaction on a second aromatic ring (i.e. intramolecular homolytic arylation) are rare and not synthetically useful.64-158-161... 

Scheme 22 presents some selected aryl radical cyclizations. The first example shows that isomerization of the intermediate radicals is again a concern. This isomerization, which is usually called the neo-phyl rearrangement,101 is promoted by the activating aldehyde group in the case at hand.102-103 The other examples illustrate that aryl radical cyclizations provide practical routes to benzo-fused heterocycles.104-105... 

Although the bimolecular additions of aryl radicals to aromatic rings are not useful due to a lack of selectivity, the corresponding cyclizations are useful for constructing biaryl bonds. Equation (5) provides a generalized example of the Pschorr reaction.172 This cyclization of a diazonium salt is one of the classical methods for biaryl bond formation, and there are a variety of related reactions.138... 

For an analysis of the relative reactivity of vinyl and aryl radicals towards cyclization and hydrogen abstraction from tin hydride, see ref. 34, p. 429. 

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